1. Field of the Invention
The present invention relates to a method for producing L-cysteine or a related substance thereof. More precisely, the present invention relates to a bacterium suitable for production of L-cysteine or a related substance thereof, and a method for producing L-cysteine or a related substance thereof utilizing the bacterium. L-cysteine and related substances thereof are useful in the fields of drugs, cosmetics, and foods.
2. Brief Description of the Related Art
L-cysteine is conventionally obtained by extraction from keratin-containing substances such as hair, horns, and feathers, or by converting the precursor DL-2-aminothiazoline-4-carboxylic acid using a microbial enzyme. L-cysteine has been produced on a large scale by an immobilized enzyme method utilizing a novel enzyme. Furthermore, it has also been attempted to produce L-cysteine by fermentation utilizing a microorganism.
As microorganisms having the ability to produce L-cysteine, a coryneform bacterium is known, for example, in which intracellular serine acetyltransferase activity is increased (Japanese Patent Laid-open (Kokai) No. 2002-233384). A technique has been reported of increasing L-cysteine-producing ability by incorporating a mutant serine acetyltransferase of which feedback inhibition by L-cysteine is attenuated (Japanese Patent Laid-open (Kokai) No. 11-155571, U.S. Patent Published Application No. 20050112731, and U.S. Pat. No. 6,218,168).
Furthermore, as microorganisms in which L-cysteine-producing ability is enhanced by suppressing the system which acts to decompose L-cysteine, there are known coryneform bacteria or Escherichia bacteria in which the activity of cystathionine-β-lyase (Japanese Patent Laid-open (Kokai) No. 11-155571), tryptophanase (Japanese Patent Laid-open (Kokai) No. 2003-169668), or O-acetylserine sulfhydrylase B (Japanese Patent Laid-open (Kokai) No. 2005-245311) is attenuated or deleted.
Moreover, it is known that the ydeD gene coding for the YdeD protein participates in secretion of metabolic products of the L-cysteine pathway (Dassler et al., Mol. Microbiol., 36, 1101-1112 (2000)). Furthermore, techniques have been reported of enhancing L-cysteine-producing ability by increasing expression of the mar locus, emr locus, acr locus, cmr locus, mex gene, bmr gene or qacA gene (U.S. Pat. No. 5,972,663), or emrAB, emrKY, yojIH, acrEF, bcr or cusA gene (Japanese Patent Laid-open (Kokai) No. 2005-287333). These loci/genes code for proteins which are able to secrete a cytotoxic substance from the cells.
Furthermore, an Escherichia coli is known to produce L-cysteine, in which the activity of the positive transcriptional control factor of the cysteine regulon encoded by the cysB gene is increased (International Patent Publication WO01/27307).
Furthermore, a mutant serA coding for 3-phosphoglycerate dehydrogenase is known, of which feedback inhibition by serine is attenuated, and use thereof for L-cysteine production by Escherichia coli has been suggested (U.S. Pat. No. 5,856,148 and U.S. Patent Published Application No. 20050009162).
Although yciW is registered in the database EcoCyc as a gene coding for a predicted oxidoreductase (BioCyc Home Page, Escherichia coli K-12-substr. MG1655 Gene: yciW [searched on Oct. 14, 2009], Internet URL >biocyc (dot) org/ECOLI/NEW-IMAGE?type=GENE&object=G6640>), the actual functions thereof are unknown, and the relation thereof with L-cysteine production is not known.
Moreover, although it has been reported that the yciW gene is up-regulated by depletion of a sulfur source (Gyaneshwar, P. et al., J. Bacteriol., 187:1074-1090 (2005)), furfural (Elliot N., Miller, E. N., et al., Appl. Envir. Microbiol., 10.1128-/AEM.01187-09 (2009)), and oxidative stress (Wang, S., et al., Appl. Envir. Microbiol., 10.1128/AEM.00914-09 (2009)), it is mentioned in all the documents only as one of a large number of genes that showed variation of expression in microarray experiments, and relation thereof with L-cysteine production has not been suggested.